Cancer, known medically as a malignant neoplasm, is a broad group of diseases involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invading nearby parts of the body. The cancer may also spread to more distant parts of the body through the lymphatic system or bloodstream. Not all tumors are cancerous; benign tumors do not invade neighboring tissues and do not spread throughout the body. There are over 200 different known cancers that affect humans.
Cancer can be detected in a number of ways, including the presence of certain signs and symptoms, screening tests, or medical imaging. Once a possible cancer is detected it is usually diagnosed by microscopic examination of a tissue sample from a tissue biopsy. Detecting and diagnosing cancers early on is essential when it comes to treatment outcome and survival, especially when it comes to highly malignant tumors.
Carcinoma, also often denoted epithelial cancer in the art, the most common type of malignant neoplasia (cancer) occurring in humans, is a tumor tissue derived from putative epithelial cells whose genome has become altered or damaged to such an extent that the cells become transformed, and begin to exhibit abnormal malignant properties. Carcinomas can be diagnosed through biopsy, including fine-needle aspiration (FNA), core needle biopsy, or surgical biopsy. Microscopic examination by a pathologist is necessary to identify cellular or tissue architectural characteristics as well as tissue specific biomarker patterns.
Increasing evidence indicates that diagnostic biopsies of possible cancers may induce tumor cell dissemination and subsequently distant metastases. There is therefore an urgent need to substitute the hazardous tumor tissue sampling biopsy procedures by diagnostic methods not traumatizing the tumor tissue causing cancer spread, but still having the possibility to detect and diagnose cancer early on. A patient friendly, simple and risk-free detection and diagnosis of cancer and cancer status is therefore needed. Especially regarding the most highly malignant cancers, ovarian, pancreatic and colorectal, it is very desirable to be able to perform an early non-invasive diagnosis to save lives. Also, to be able to diagnose malignant prostate cancer with a non-invasive procedure would be very beneficial, since taking prostate biopsies are particularly problematic. All these cancers are typically classified carcinoma, i.e. cancers of epithelial cell origin.
Ovarian cancer is a cancerous growth arising from the ovary, wherein suspected cancer needs to be confirmed with surgery to inspect the abdominal cavity, biopsies and detection of cancer cells in the abdominal fluid. These procedures are both cumbersome and risky for the patient. Due to asymptomatic development, ovarian cancer is often diagnosed at an advanced stage, with a poor prognosis. An easily performed test that could confirm cancer and cancer status would therefore be very beneficial for the diagnosis of ovarian cancers.
Most ovarian cancers are classified as “epithelial” and arise from the epithelium of the ovary. Epithelial ovarian cancer (EOC) is the deadliest of all gynaecologic malignancies-EOC develops asymptomatically, and is in the majority of cases detected at an advanced stage. Due to its notorious capability for asymptomatic growth and spread in the abdominal cavity, curative treatment is then difficult to achieve. Tumour markers for EOC (e.g. CA-125) are in clinical use today. Due to the low specificity they are only used as supportive information together with ultrasound and physical examination, but offer limited sensitivity. Measuring the levels of CA-125 has bigger value during the monitoring during treatment of ovarian cancer. For example, in one study, CA-125 was used in the assessment of patients presenting with a pelvic mass. Elevated CA-125 levels had a sensitivity of 72% and specificity of 78% for ovarian cancer (positive predictive value of 72% and a negative predictive value of 78%). However, in another study, sensitivity for early-stage disease was only 40% (Skates S J, et al. Preoperative sensitivity and specificity for early-stage ovarian cancer when combining cancer antigen CA-125II, CA 15-3, CA 72-4, and macrophage colony-stimulating factor using mixtures of multivariate normal distributions.
Preoperative biopsy and other rupturing injury of suspect cancer lesions are strongly contraindicated due to the high risk of spread of EOC. Instead, expert gynaecologic ultrasound is the method of choice in assessment of adnexal masses. However, in many cases even an experienced medical examiner cannot provide conclusive answers.
To reach significant progress, there is an urgent need to improve the means for early detection of EOC, and following detection, the means to discriminate benign and malignant lesions, as a prerequisite for a differentiated optimized treatment.
Trombocytosis is a common observation in patients with progressing cancer, and has also been specifically associated with worse prognosis and early relapse in patients operated for non-advanced EOC. There is also increasing, intriguing evidence that platelets, beyond their participation in hemostasis, can influence angiogenic and immunological processes and thereby decisively contribute to tumor development.
Proteomic analyses of platelets have shown that angiogenic factors can be sequestered by platelets, and then specifically released and delivered to sites of activated endothelium within early tumours. A so-called “metastatic/malignant platelet phenotype” could be observed in patients with different newly diagnosed metastatic diseases.
Prostate cancer is a type of cancer that develops in epithelial prostate tissue. Today prostate cancer is diagnosed using prostate-specific antigen (PSA). This is merely an indicative method and is not specific for malignant cancer. Due to this fact there is always multiple biopsies taken for confirmatory diagnosis. Taking biopsies is unpleasant for the patient and reported to be associated with serious side effects. Several patients have to visit the emergency room even the same day for sepsis as an effect from the biopsy. Impotency is also a side effect that is rather frequent. The most dangerous effect longer term is that cancer cells actually leak out from the prostate gland during the biopsy. These cancer cells can then spread and potentially cause metastasis. In prostate cancer about 70% are of low malignancy and not in need of immediate or aggressive treatment. Therefore, tests that can indicate cancer, and also can distinguish the high malignancies from the low malignancies are highly sought after. It is within the scope of the invention to provide a test that can fulfil these criteria. The global incidence of prostate cancer is about 900,000 per year. If all of these were tested using the test of the invention, about 600,000 men per year would not have to be tested using unpleasant and potentially harmful biopsies. Thus, a way to diagnose prostate cancer without the need of a biopsy is desirable.
Pancreatic cancer is a malignant neoplasm originating from transformed cells arising in tissues forming the pancreas. The most common type of pancreatic cancer, accounting for 95% of these tumors, is adenocarcinoma (tumors exhibiting glandular architecture on light microscopy) arising within the exocrine component of the pancreas. A minority arises from islet cells, and are classified as neuroendocrine tumors. The signs and symptoms that eventually lead to the diagnosis depend on the location, the size, and the tissue type of the tumor, and may include abdominal pain, lower back pain, and jaundice (if the tumor compresses the bile duct), unexplained weight loss, and digestive problems. Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States and the eighth worldwide. Pancreatic cancer has an extremely poor prognosis: for all stages combined, the 1- and 5-year relative survival rates are 25% and 6%, respectively; for local disease the 5-year survival is approximately 15% while the median survival for locally advanced and for metastatic disease, which collectively represent over 80% of individuals, is about 10 and 6 months, respectively. Individuals vary, however—some are only diagnosed when they are already terminally ill and therefore only have a few days or weeks. Others have slower progression and may live a couple of years even if surgery is not possible. Men are 30% more likely to get pancreatic cancer than are women.
Pancreatic cancer is one of the most lethal malignancies worldwide and thus demonstrates an urgent demand for improved screening tools for early detection. Diagnosis of pancreatic cancer at early stages is crucial because successful surgery at early tumor stages is the only curative therapy today. Only 10-30% of pancreatic tumor patients are operated with curative intend, and of theses, only half actually undergo RO resection. The expected 5-year survival rate of RO resected patients with additional adjuvant chemotherapy is about 4-26%.
A diagnostic test for early detection is here highly sought after. The challenge is to find if there is a time-window between the start of the cancer in the body and before it is too late for starting treatment. If this window is big enough a diagnostic method is extremely valuable. Due to the high malignancy and aggression of the disease, it is highly desirable to find a way to diagnose pancreatic cancer early, preferably without the hazardous procedure of taking a biopsy.
Colorectal cancer, also known as colon cancer, rectal cancer, or bowel cancer, is a cancer from uncontrolled cell growth in the colon or rectum (parts of the large intestine), or in the appendix. Genetic analysis shows that essentially colon and rectal tumours are genetically the same cancer. Symptoms of colorectal cancer typically include rectal bleeding and anemia which are sometimes associated with weight loss and changes in bowel habits. Most colorectal cancer occurs due to lifestyle and increasing age with only a minority of cases associated with underlying genetic disorders. It typically starts in the lining of the bowel and if left untreated, can grow into the muscle layers underneath, and then through the bowel wall. Screening is effective at decreasing the chance of dying from colorectal cancer and is recommended starting at the age of 50 and continuing until a person is 75 years old. Localized bowel cancer is usually diagnosed through sigmoidoscopy or colonoscopy. Cancers that are confined within the wall of the colon are often curable with surgery while cancer that has spread widely around the body is usually not curable and management then focuses on extending the person's life via chemotherapy and improving quality of life. Colorectal cancer is the third most commonly diagnosed cancer in the world, but it is more common in developed countries. Around 60% of cases were diagnosed in the developed world. It is estimated that worldwide, in 2008, 1.23 million new cases of colorectal cancer were clinically diagnosed, and that it killed 608,000 people.
Colon cancer ranks among the most frequent malignancies and is the fourth leading cause of cancer-related death worldwide. Detection of colon cancer at early stages is critical for curative treatment interventions: although the 5-year disease-free survival for International Union Against Cancer (UICC) stage I tumors exceeds 90%, this rate is reduced to 63% in UICC III and <5% in UICC IV carcinomas. Yet, despite the implementation of current screening programs about 50% of these malignancies are detected at advanced tumor stages. Colorectal cancer is today diagnosed using imaging techniques combined with colonoscopy. There are biomarker tests are available in the market, but none of these biomarker tests are good enough for use in clinical diagnostics. Thus, it would also be highly desirable to find a way to diagnose pancreatic cancer early, preferably without the riskful procedure of taking a biopsy.
There is therefore a general need for a technology enabling early detection of cancer since it would allow for a more effective treatment of patients and hence a higher survival rate. Further, it would also be beneficial if the technology can be used to determine the progression of the cancer, i.e. if it is in an early or advanced stage since early, often local, or advanced, often disseminated malignancies, require different treatment alternatives, and are characterized by a different prognosis.
U.S. Pat. No. 8,173,433 describes an early detection of clinical conditions having associated changes in systemic angiogenic activity, particularly cancers, inflammatory conditions, infections, and events associated with pregnancy and abortion.